Reaction of 4-(2′-hydroxyaryl)-1,3-dithiolium salts with sodium sulfide. A selective synthesis of 2′-hydroxyacetophenones

Article abstract of DOI:10.1081/SCC-120022483

The treatment of 4-(2′-hydroxyaryl)-2-(N,N-dialkylamino)-1,3-dithiolium perchlorates (1a-g) with sodium sulfide nonahydrate in ethanol at room temperature affords the corresponding 1,3-dithiole-2-thiones (2a-g). When these reactions are conducted in boiling ethanol, 2′-hydroxyacetophenones (3a-g) have been obtained in good to excellent yield. A tentative mechanism for the formation of 3a-g shows that this reaction is regioselective, this being established by the presence of hydroxyl group in 2′-position. That has been confirmed in a control experiment, 4-phenyl-2-(piperidin-1-yl)-1,3-dithiolium perchlorate affording a mixture of condensation products of acetophenone and phenylacetaldehyde, under similar reaction conditions.

Full text of DOI:10.1081/SCC-120022483

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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 17, pp. 3071–3076, 2003
Reaction of 4-(20-Hydroxyaryl)-1,3-dithiolium
Salts with Sodium Sulfide. ASelective Synthesis
of 20-Hydroxyacetophenones
*
Mihail Lucian Birsa
Department of Organic Chemistry, Faculty of
Chemistry, ‘‘Al.I. Cuza’’ University of Iasi, Romania
ABSTRACT
The treatment of 4-(20-hydroxyaryl)-2-(N,N-dialkylamino)-1,3-
dithioliumperchlorates ( 1a–g) with sodiumsulfide nonahydrate in
ethanol at roomtemperature affords the corresponding 1,3-dithiole-
2-thiones (2a–g). When these reactions are conducted in boiling etha-
nol, 20-hydroxyacetophenones (3a–g) have been obtained in good
to excellent yield. A tentative mechanism for the formation of 3a–g
shows that this reaction is regioselective, this being established by the
presence of hydroxyl group in 20-position. That has been confirmed
in a control experiment, 4-phenyl-2-(piperidin-1-yl)-1,3-dithiolium
perchlorate affording a mixture of condensation products of aceto-
phenone and phenylacetaldehyde, under similar reaction conditions.
*Correspondence: Mihail Lucian Birsa, Department of Organic Chemistry,
Faculty of Chemistry, ‘‘Al.I. Cuza’’ University of Iasi, 11 Bd. Carol I, 6600
Iasi-6, Romania; Fax: þ40 232 201313; E-mail: lbirsa@uaic.ro.
3071
DOI: 10.1081/SCC-120022483
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3072
Birsa
Key Words: 1,3-Dithioliumsalts; Sodiumsulfide; 1,3-Dithiole-2-
thiones; 20-Hydroxyacetophenones.
1,3-Dithioliumsalts are well known precursors for tetrathiafulva-
lenes, compounds with wide applications in advanced materials.[1,2]
An important synthetic pathway for conversion of 2-substituted 1,3-
dithioliumsalts to the corresponding tetrathiafulvalenes takes place via
1,3-dithiole-2-thiones.[3–6] However, the chemistry of 1,3-dithiolium
salts has not only been focused in tetrathiafulvalenes preparation, the
electrophilic properties of 2-C atomopening the way for a rather
interesting chemistry. The chemical properties of 1,3-dithiolium salts
have been well reviewed.[7,8]
We wish to report here an investigation on the reaction of
some 4-(20-hydroxyaryl)-2-(N,N-dialkylamino)-1,3-dithiolium salts with
sodiumsulfide. Although investigations in this area appear to have a
low interest, since it is well known that reaction of 1,3-dithioliumsalts
with sodiumsulfide provides 1,3-dithiole-2-thiones, this study is based
on a previous finding of our group,[9] which showed that 30,50-dichloro-20-
hydroxyacetophenone is formed from the reaction of sodium sulfide with
4-(30,50-dichloro-20-hydroxy-phenyl)-2-(N,N-dimethylamino)-1,3-dithiolium
perchlorate, in refluxing ethanol. We have decided to extend these
reactions to various substituted 4-(20-hydroxyaryl)-2-(N,N-dialkyla-
mino)-1,3-dithiolium salts (1a–g, NR2¼ pyrrolydine, piperidine, morpho-
line) and to elucidate some mechanistic aspects. As expected, the
treatment of 1,3-dithiolium salts 1a–g[10,11] with an excess of sodium
sulfide nonahydrate in ethanol at roomtemperature affords the corre-
sponding 1,3-dithiole-2-thiones 2a–g (Sch. 1). These compounds have
been isolated as yellow crystalline products in good to excellent yields
(Table 1).
Unlike the above, when reactions are conducted in refluxing ethanol
the corresponding substituted 20-hydroxyacetophenones 3a–g are formed
in good yields (Sch. 1). All 20-hydroxyacetophenones 3a–g are known
compounds and their analytical data are in accordance with those
reported. A first assumption indicates that the formation of 3a–g takes
place via 1,3-dithiole-2-thiones 2. Indeed, when the reaction of the latter
with an excess of sodiumsulfide has been conducted in refluxing ethanol,
acetophenones 3 have been isolated in similar yields (Sch. 1). This
shows that in a first step trithiones 2 undergo a nucleophilic attack
of sulfide anion. We assume that ring opening of a 1,3-dithiole derivative
is followed by carbon disulfide elimination. The carbon disulfide elimina-
tion has been proved by its quenching with secondary amines (piperidine,

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4-(20-Hydroxyaryl)-1,3-dithiolium Salts
3073
R
R
S
S
S
S
O
N
S
1. Na2S·9H2O
EtOH, rt, 2h
R1
R1
R1
1. Na2S·9H2O
EtOH, reflux, 1h
2. H2O, HCl
79-98%
2. H2O, HCl
71-79%
ClO4
OH
1a-g
OH
2a-g
1. Na2S·9H2O, EtOH, reflux, 1h; 2. H2O, HCl; 71-79%
OH
R2
R2
R2
3a-g
1,2,3
a
b
c
d
e
f
g
R1
R2
H
H
Br
H
Br
Br
CH3
H
CH3
Br
Br
CH3
I
I
Scheme 1.
morpholine). The reaction of 1,3-dithiolium salts 1a–g with sodium
sulfide nonahydrate under refluxing ethanol appears to be a complete
regioselective one. This assumption has been proved in a control
experiment, the treatment of 4-phenyl-2-(piperidin-1-yl)-1,3-dithiolium
perchlorate with sodiumsulfide nonahydride under similar reaction
conditions (Sch. 2). A mixture of acetophenone and phenylacetaldehyde
has resulted, compounds that undergo condensation reactions
under the basic reaction conditions. A solid product has been
isolated (both acetophenone as well as phenylacetaldehyde are liquids
at room temperature), whose NMR analysis indicates that a mixture
of aldol and dehydrated aldol addition products of the latter has been
formed.
No experimental evidence in support of a detailed mechanism for
the conversion of 1,3-dithioliumsalts 1a–g into 20-hydroxyacetophenones
3a–g was obtained. However, the regioselectivity of this reaction
appears to be established by the presence of hydroxyl group in 20
position.
In conclusion, we assume that reaction of 4-(20-hydroxyaryl)-2-
(N,N-dialkylamino)-1,3-dithiolium salts with sodium sulfide nona-
hydrate in boiling ethanol can be an alternative method for the synthesis
of substituted 20-hydroxyacetophenones. This reaction takes place via
carbon disulfide extrusion, the selective formation of 20-hydroxy-
acetophenones being established by the presence of hydroxyl group in
20-position.

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3074
Birsa

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4-(20-Hydroxyaryl)-1,3-dithiolium Salts
3075
O
C6H5
S
CH3
Na2S 9H2O, EtOH
N
condensation products
O
H
S
reflux, 1h
C6H5
ClO4
C6H5 CH2
Scheme 2.
EXPERIMENTAL
Melting points were obtained on a Mel-Temp II apparatus and are
1
uncorrected. H NMR and 13C NMR spectra were recorded on a Bruker
DPX-300 spectrometer in DMSO-d6. IR spectra were recorded on a
Digilab FTS-40 spectrometer in KBr pellets.
General Procedure for 4-(20-Hydroxyaryl)-1,3-dithiole-2-
thiones 2a–g
To a suspension of 4-(20-hydroxyaryl)-2-(N,N-dialkylamino)-1,3-
dithioliumperchlorate ( 1a–g) (10 mmol) in EtOH (96%, 100 mL),
Na2S ꢁ 9H2O (30 mmol) was added. The reaction mixture was stirred
at r.t. until a homogeneous solution was obtained (ca. 2 h) and then
poured into water (200 mL) and treated with HCl (37%) to pH ¼ 1.
The resulted precipitate was filtered, washed with water, dried, and
recrystallized fromMeOH (45–50 mL/g). Analytical data of
presented in Table 1.
2a–g are
General Procedure for 20-Hydroxyarylacetophenones 3a–g
To a suspension of 4-(20-hydroxyaryl)-2-(N,N-dialkylamino)-1,3-
dithioliumperchlorate
( 1a–g) (5 mmol) in EtOH (96%, 50 mL),
Na2S ꢁ 9H2O (12.5 mmol) was added. The reaction mixture was heated
at reflux temperature for 1 h and then poured into 1:1 HCl solution
(200 mL). The crude reaction product was separated and purified by
column chromatography (3a) or recrystallization (3b–g). In the same
experimental conditions 1,3-dithiole-2-thiones (2a–g) gave 3a–g. The
analytical data of 20-hydroxyacetophenones are in accordance with
those reported.

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3076
Birsa
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Received in the Netherlands November 17, 2002

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